Patient-Level Exposure to Actionable Pharmacogenomic Medications in a Nationally Representative Insurance Claims Database.

BACKGROUND: The prevalence of exposure to pharmacogenomic medications is well established but little is known about how long patients are exposed to these medications. AIM: Our objective was to describe the amount of exposure to actionable pharmacogenomic medications using patient-level measures among a large nationally representative population using an insurance claims database. METHODS: Our retrospective cohort study included adults (18+ years) from the IQVIA PharMetrics® Plus for Academics claims database with incident fills of 72 Clinical Pharmacogenetics Implementation Consortium level A, A/B, or B medications from January 2012 through September 2018. Patient-level outcomes included the proportion of days covered (PDC), number of fills, and average days supplied per fill over a 12-month period. RESULTS: Over 1 million fills of pharmacogenetic medications were identified for 605,355 unique patients. The mean PDC for all medications was 0.21 (SD 0.3), suggesting patients were exposed 21% (77 days) of the year. Medications with the highest PDC (0.55-0.89) included ivacaftor, tamoxifen, clopidogrel, HIV medications, transplant medications, and statins; with the exception of statins, these medications were initiated by fewer patients. Pharmacogenomic medications were filled an average of 2.8 times (SD 3.0, range 1-81) during the year following the medication's initiation, and the average days supplied for each fill was 22.3 days (SD 22.4, range 1-180 days). CONCLUSION: Patient characteristics associated with more medication exposure were male sex, older age, and comorbid chronic conditions. Prescription fill data provide patient-level exposure metrics that can further our understanding of pharmacogenomic medication utilization and help inform opportunities for pharmacogenomic testing.

Postintubation Sedation Practices Within Multiple Emergency Departments Across a Large Pediatric Health Care Organization.

OBJECTIVE: Children requiring rapid or standard sequence intubation are at risk of experiencing paralysis without adequate sedation when the duration of neuromuscular blockade exceeds the duration of sedation provided by the induction agent. The objective of this study was to evaluate the rate of appropriately timed postintubation sedation (PIS; defined as the administration of PIS before the clinical effects of the induction agent have dissipated) in patients requiring intubation across multiple emergency department/urgent care sites within a large pediatric health care organization. METHODS: This retrospective cohort study included patients admitted to 1 of 6 affiliated pediatric emergency department or urgent care sites who were intubated with an induction agent and neuromuscular blocker between January 2016 and December 2021. Patients were excluded if they were intubated in the setting of status epilepticus or cardiac arrest. Stepwise logistic regression identified factors associated with appropriately timed PIS. RESULTS: A total of 283 patients met the inclusion criteria (mean age, 8 ± 7.6 years; 56% male). Two hundred thirty-eight patients (83%) received some form of PIS (105 [37%] received appropriately timed PIS and 133 [47%] received delayed PIS), and 45 patients (16%) received no PIS. The median time to receive PIS following administration of the induction agent was 21 minutes (interquartile range, 11-40 minutes). Patients induced with fentanyl were the least likely to receive PIS, whereas patients induced with etomidate were the most likely. However, because of the short duration of etomidate, most patients induced with etomidate failed to receive PIS in a timely manner. CONCLUSIONS: Delayed PIS is common and may result in periods of ongoing paralysis without adequate sedation. Emergency department providers and pharmacists must recognize the brevity of some induction agents and provide more timely PIS.

Cost-Effectiveness Analysis of New Beta-Lactam Beta-Lactamase Inhibitor Antibiotics Versus Colistin for the Treatment of Carbapenem-Resistant Infections.

Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.

Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab.

Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. This was a retrospective observational cohort study conducted at a five hospital health system in Michigan, United States. Adult patients with confirmed COVID-19 that were admitted to the hospital and received tocilizumab for cytokine storm from March 1, 2020 through April 3, 2020 were included. Patients were grouped into survivors and non-survivors based on 28 day in-hospital mortality. Study day 0 was defined as the day tocilizumab was administered. Factors independently associated with in-hospital survival at 28 days after tocilizumab administration were assessed. Epidemiologic, demographic, laboratory, prognostic scores, treatment, and outcome data were collected and analyzed. Clinical response was collected and defined as a decline of two levels on a six-point ordinal scale of clinical status or discharged alive from the hospital. Of the 81 patients included, the median age was 64 (58-71) years and 56 (69.1%) were male. The 28 day in-hospital mortality was 43.2%. There were 46 (56.8%) patients in the survivors and 35 (43.2%) in the non-survivors group. On study day 0 no differences were noted in demographics, clinical characteristics, severity of illness scores, or treatments received between survivors and non-survivors. C-reactive protein was significantly higher in the non-survivors compared to survivors. Compared to non-survivors, recipients of tocilizumab within 12 days of symptom onset was independently associated with survival (adjusted OR: 0.296, 95% CI: 0.098-0.889). SOFA score ≥8 on day 0 was independently associated with mortality (adjusted OR: 2.842, 95% CI: 1.042-7.753). Clinical response occurred more commonly in survivors than non-survivors (80.4% vs. 5.7%; p < 0.001). Improvements in the six-point ordinal scale and SOFA score were observed in survivors after tocilizumab. Early receipt of tocilizumab in patients with severe COVID-19 was an independent predictor for in-hospital survival at 28 days.

Discharge Delays and Costs Associated With Outpatient Parenteral Antimicrobial Therapy for High-Priced Antibiotics.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is a widely used, safe, and cost-effective treatment. Most public and private insurance providers require prior authorization (PA) for OPAT, yet the impact of the inpatient PA process is not known. Our aim was to characterize discharge barriers and PA delays associated with high-priced OPAT antibiotics. METHODS: This was an institutional review board-approved study of adult patients discharged with daptomycin, ceftaroline, ertapenem, and novel beta-lactam-beta-lactamase inhibitor combinations from January 2017 to December 2017. Patients with an OPAT PA delay were compared with patients without a delay. The primary endpoint was total direct hospital costs from the start of treatment. RESULTS: Two-hundred patients were included: 141 (71%) no OPAT delay vs 59 (30%) OPAT delay. More patients with a PA delay were discharged to a subacute care facility compared with an outpatient setting: 37 (63%) vs 52 (37%), P = .001. Discharge delays and median total direct hospital costs were higher for patients with OPAT delays: 31 (53%) vs 21 (15%), P < .001 and $19 576 (interquartile range [IQR], 10 056-37 038) vs $7770 (IQR, 3031-13 974), P < .001. In multiple variable regression, discharge to a subacute care facility was associated with an increased odds of discharge delay, age >64 years was associated with a decreased odds of discharge delay. CONCLUSIONS: OPAT with high-priced antibiotics requires significant care coordination. PA delays are common and contribute to discharge delays. OPAT transitions of care represent an opportunity to improve patient care and address access barriers.

Improving care for critically ill patients with community-acquired pneumonia.

PURPOSE: The purpose of this study was to improve antimicrobial management and outcomes of critically ill patients with community-acquired pneumonia (CAP) through implementation of a pharmacist-driven bundle for ordering evidence-based diagnostic tests in a medical intensive care unit (MICU). METHODS: An inpatient collaborative practice agreement (CPA) was established for MICU pharmacists to order criteria-driven diagnostic testing for CAP from November 2017-March 2018. Adults admitted to the MICU and started on empiric antibiotics for CAP were included. The intervention arm was compared with a standard of care (SOC) group from November 2016-March 2017. RESULTS: Ninety-one patients were included in each group. There was no difference in the median antibiotic duration between SOC and CPA, at 7 days (interquartile range [IQR], 6-10) versus 7 days (IQR, 6-8), respectively. The overall use of evidence-based diagnostic tests increased in the CPA group. Patients in the CPA group had more frequent pathogen identification (SOC and CPA, respectively: 31 [34%] versus 46 [51%], p = 0.035) and antimicrobial deescalation (24 [26%] versus 53 [58%], p < 0.001). There was no significant difference in length of intensive care unit stay, at 4 days for SOC (IQR, 2-10) versus 6 days for CPA (IQR, 3-10), and no significant difference in inpatient all-cause mortality (13 [14%] versus 7 [8%]), retreatment 14 [15%] versus 11 [12%]), or 30-day readmission 16 ([18%] versus 13 [14%]) for SOC and CPA, respectively. The CPA was the only variable that was independently associated with antimicrobial deescalation (odds ratio, 4.030; 95% confidence interval, 2.101-7.731) in a multiple logistic regression. CONCLUSION: Implementation of a pharmacy-driven pneumonia diagnostic stewardship bundle improved the use of evidence-based diagnostics and increased the frequency of pathogen identification. This intervention was associated with increased antimicrobial deescalation without a negative impact on patient safety outcomes.